Methods of detecting one or more analytes in a sample are generally known in the art. Typically, test elements are employed in interaction with analytical apparatuses that evaluate the test elements. Test elements generally have at least one test chemical, which can be at least one detection reagent for qualitatively and/or quantitatively detecting the analyte.
A great technical challenge with known test elements is stability of the test chemicals. For example, oxygen and moisture can impair quality of test chemicals or of parts thereof. In the art, considerable efforts are known to stabilize test chemicals against such influences and to lower requirements for storage of the test elements and to increase long-term stability. For example, Int'l Patent Application Publication No. WO 2007/012494 describes a test chemical containing stable NAD/NADH derivatives.
Likewise, EP Patent Application Publication No. 2093284 describes stabilizing dehydrogenases with stable coenzymes.
Moreover, EP Patent Application Publication No. 1189064 describes a method of controlling suitability of use of test elements. In the reference, a deviation of a ratio of a control value and a first standard reference value from a first reference ratio is checked, which is formed from a control reference value and a first standard reference value. A checked test element is rejected if the deviation lies outside a pre-specified tolerance range. It is proposed therein the usability of a test element with the aid of a so-called dry blank value measurement of a test field (i.e., an optical measurement of a test field still not wetted with sample fluid). To carry out the control method, it is further proposed that the test element, in addition to having a test field serving for the control of its suitability for use and for carrying out the analysis, contains an integrated reference control means. This method, however, has numerous challenges in practice. For example, the dry blank value measurement, in which a reflectance of the test field is measured before wetting with the sample, provides only a rough check of aging of the test element. In this manner, and within very rough limits, degraded test elements can be excluded with the aid of a discoloration of the test field, which is attributed to a discoloration of a dye contained in the test field. Furthermore, the integrated reference control means places technical demands on the design of the test elements, which are not simply and inexpensively realizable in all cases.
EP Patent Application Publication No. 2221608 describes a method of investigating a body fluid by means of a test tape. To increase measuring reliability, it is proposed therein that a control value is determined from a time- and/or wavelength-dependent change of measurement signals over a duration of a measuring time interval. With the aid of the control value, measurement signals are processed as valid or are discarded as erroneous after measurement. It also is proposed that a test field control value can be determined from a blank value measurement of still unused test fields and the usability of the test field by comparison with a batch control value to discern an influence of the storage time on the test material. It further is proposed to store the batch control value on a storage means assigned to the test tape. This method, however, has numerous challenges in practice. For example, the batch control value is attached to the test elements. In addition, rough degradations of a test chemical also are discernible by a reflectance measurement of a dry blank value, which can be attributed to degradation of a dye and a color change of the test fields connected therewith. Degradations, which are not discernible in this way and which, for example, do not lead to a color change of the test fields, can only be identified and excluded with comparative difficulty.
Int'l Patent Application Publication No. WO 2001/060248 describes methods and devices for non-invasively measuring analyte concentrations, such as glucose, in tissue. In the proposed methods, a target within the tissue of a patient is optically stimulated, the fluorescence of which correlates with the glucose concentration. It is proposed therein to use pepsin digestible collagen cross links (PDCCL) as a target. Glucose itself has a low intrinsic fluorescence, whereas fluorescence of PDCCL changes depending on the glucose concentration in the tissue of the patient. It also discloses that fluorescence of the target can be dependent on certain effects such as, for example, age, UV exposure, skin color or other effects. Accordingly, it is proposed to use fluorescence signals of the skin with irradiation in the ultraviolet spectral range (UVA) to assess and to take into consideration the state of the collagen matrix.
DE Patent Application Publication No. 10 2008 056583 describes a method and a device for determining reagent quality. In the proposed methods, a carrier element is passed through treatment stations with a test material simultaneously with certain objects. The changes of the test material are recorded and compared with reference data. It is proposed therein to record characteristic properties of the test material caused by the treatment by means of fluorescence.
Int'l Patent Application Publication No. WO 2003/023356 describes methods and devices for non-invasively measuring analyte concentrations in vivo. In the proposed devices, an optical coupler is used to connect a skin surface with a device having a multiplicity of zones. These zones include areas for a multiplicity of purposes, including a calibration of the device, a reading of the skin surface, and a protective function for the device.
The use of fluorophores for detecting glucose concentrations in test strips also is generally known in the art. See, e.g., EP Patent Application Publication No. 1780288 and Int'l Patent Application Publication No. WO 2009/015870. Specifically, glucose-induced changes in fluorescence of proteins and other fluorophores can be used for detecting glucose. See, Pickup et al. (2005) Biosens. Bioelectron. 20:2555-2565.
Likewise, the lifetime of alcohol dehydrogenase can be measured by measuring NADH formed in a detection reaction. See, Moore et al. (2004) Biomacromolecules 5:1241-1247.
Moreover, urea is known to change of intrinsic fluorescence properties of proteins with their conformation. See, Scognamiglio et al. (2004) J. Fluoresc. 14:491-498; and Mendoza-Hernandez et al. (2000) Biochim. Biophys. Acta 1478:221-231. Tryptophan also is known to change intrinsic fluorescence of proteins. See, van Duffelen et al. (2004) Biophys. J. 87:1767-1775; Bhaumik & Sonawat (1999) Physiol. Chem. Phys. Med. NMR 31:85-82; and Mendoza-Hernandez et al. (2000). Similarly, a change of a fluorescence emission of GlucDH-S is known. See, Hilt et al. (1991) Biochim. Biophys. Acta 1076:298-304. It is further known that degeneration of GlucDH with urea is reversible. See, Mendoza-Hernandez et al. (2000); and Pauly & Pfleiderer (1977) Biochem. 16:4599-4604. Absorption measurements on GlucDH also are described in Yamazaki et al. (1999) App. Biochem. Biotech. 325:77-79, wherein an absorption peak was observed at 409 nm. Temperature stress of GlucDH led to the disappearance of this absorption peak. Furthermore, fluorescence was observed, which decreased on a temperature treatment and which was attributed to an unknown cofactor. It was later discovered that the intrinsic fluorescence was caused by FAD. See, Inose et al. (2003) Biochim. Biophys. Acta 1645:133-138.
Despite the advances achieved using known detection methods, apparatuses and test chemicals, there still is a residual uncertainty with respect to an aging phenomena of the test elements. This disadvantage presently is address via test elements that are marketed as individual test strips or as test elements with several test chemical areas having an expiry date. By means of a corresponding coding, analytical apparatuses can also recognize whether this expiry date has been exceeded and correspondingly prevent use of aged test elements of this type. Nevertheless, there is the risk, even before expiry of the nominal lifespan, that defective or aged test elements can be used for a measurement. To further address the disadvantage, test elements are supplied in containers in which a drying agent is contained to maintain a low-moisture atmosphere for storage. In some instances, a user is prompted to close this container immediately after removal of a test strip. However, with users having dementia or even children, it cannot always be guaranteed that such a correct treatment of the test elements actually takes place, so that a measurement using degraded test elements cannot be excluded in all details.
For the foregoing reasons, there is a need for additional apparatuses and methods for detecting degraded test elements.